Nanotechnology provides platforms to deliver medical agents to specific cells. However, the nanoparticle’s surface becomes covered with serum proteins in the blood after administration despite engineering efforts to protect it with targeting or blocking molecules. Here, we developed a strategy to identify the main interactions between nanoparticle-adsorbed proteins and a cell by integrating mass spectrometry with pooled genome screens and Search Tool for the Retrieval of Interacting Genes analysis. We found that the low-density lipoprotein (LDL) receptor was responsible for approximately 75% of serum-coated gold nanoparticle uptake in U-87 MG cells. Apolipoprotein B and complement C8 proteins on the nanoparticle mediated uptake through the LDL receptor. In vivo, nanoparticle accumulation correlated with LDL receptor expression in the organs of mice. A detailed understanding of how adsorbed serum proteins bind to cell receptors will lay the groundwork for controlling the delivery of nanoparticles at the molecular level to diseased tissues for therapeutic and diagnostic applications.

纳米技术提供了将药物输送到特定细胞的平台。然而，纳米颗粒的表面在给药后被血液中的血清蛋白覆盖，尽管工程上努力通过靶向或阻断分子来保护它。在这里，我们开发了一种策略，通过将质谱与汇集基因组筛选和相互作用基因分析检索工具相结合，来识别纳米颗粒吸附的蛋白质与细胞之间的主要相互作用。我们发现低密度脂蛋白 (LDL) 受体负责 U-87 MG 细胞中大约 75% 的血清包被金纳米颗粒摄取。纳米颗粒上的载脂蛋白 B 和补体 C8 蛋白通过 LDL 受体介导摄取。体内，纳米颗粒的积累与小鼠器官中 LDL 受体的表达相关。详细了解吸附的血清蛋白如何与细胞受体结合，将为在分子水平上控制纳米粒子向患病组织的输送奠定基础，以用于治疗和诊断应用。